Method and device for infusion of pharmacologic agents and thrombus aspiration in artery

ABSTRACT

A catheter device and method for treating an artery with thrombus, the catheter comprising an inflatable member. A carrier catheter has a proximal end and a distal end adapted to be inserted percutaneously into an artery, the carrier catheter having a tubular body adjacent to a rear end of the inflatable member. An inflating tube passes through the tubular body and having an open front end in fluid communication with the inflatable member to inflate same. An infusion tube is adapted to infuse pharmacologic agents, the infusion tube passing through the tubular body and having an open front end extending beyond the inflatable member. An aspiration tube is adapted to aspire the thrombus, the aspiration tube passing through the tubular body and having an open front end between the carrier catheter and the inflatable member.

CROSS-REFERENCE TO RELATED APPLICATION

The present application claims priority on U.S. Provisional ApplicationSer. No. 61/669,934, filed on Jul. 10, 2012, and incorporated herein byreference.

FIELD OF THE DISCLOSURE

The present application pertains to a method and device for the infusionof pharmacologic agents and thrombus aspiration in atheroscleroticvascular disease.

BACKGROUND OF THE ART

Atherosclerotic vascular disease is one of the main causes of adultmortality in developed countries. The sudden occlusion of a coronaryartery subsequent to a plaque rupture remains one of the most frequentcauses of myocardial infarction.

Percutaneous coronary intervention, when performed promptly, is anefficient reperfusion method. However, there remains issues with theopening of coronary arteries. Despite efficient and prompt intervention,some patients will present a condition known as no-reflow in which, inspite of the fact that the coronary artery is opened without residualstenosis, myocardial perfusion is diminished. No-reflow may be caused bytwo distinct phenomenons. A first one is the distal embolization ofmicroparticles in blood vessels. A second phenomenon is reperfusioninjury.

It has been shown that aspiration catheters are efficient in removingblood clots from arteries in the myocardial infarction status and thusimprove the blood flow in the infarction zone. However, despite theirefficiency, such catheters do not necessarily prevent the distalembolization of microparticles subsequent to their use. Also, suchcatheters do not allow drug infusion distally to the occlusion prior tothrombus aspiration.

SUMMARY OF THE APPLICATION

It is therefore an aim of the present disclosure to provide a novelmethod for infusing pharmacologic agents and/or performing thrombusaspiration in atherosclerotic vascular disease.

It is a further aim of the present disclosure to provide a novel devicefor infusing pharmacologic agents and/or performing thrombus aspirationin atherosclerotic vascular disease.

Therefore, in accordance with a first embodiment of the presentapplication, there is provided a method for treating an artery having athrombus comprising: percutaneously positioning a catheter with aninfusion tube in the artery proximally to the thrombus; passing a tip ofthe infusion tube through the thrombus; and infusing at least onepharmacologic agent distally to the thrombus via the infusion tube.

Further in accordance with the first embodiment of the presentapplication, positioning the catheter comprises positioning aninflatable member of the catheter proximally to the thrombus, andfurther comprising inflating the inflatable member proximally to thethrombus.

Still further in accordance with the first embodiment of the presentapplication, inflating the inflatable member proximally to the thrombusis performed prior to infusing at least one pharmacologic agent distallyto the thrombus.

Still further in accordance with the first embodiment of the presentapplication, positioning the catheter further comprises positioning anaspiration tube of the catheter proximally to the thrombus, theaspiration tube being proximal to the inflatable member.

Still further in accordance with the first embodiment of the presentapplication, there is performed an aspiration via the aspiration tubewhile deflating the inflatable member to aspire the thrombus.

Still further in accordance with the first embodiment of the presentapplication, performing the aspiration is initiated before deflating theinflatable member.

Still further in accordance with the first embodiment of the presentapplication, positioning the catheter and passing of the tip are done bymoving the catheter over a guide wire.

Still further in accordance with the first embodiment of the presentapplication, moving the catheter over the guide wire comprises movingthe catheter and the infusion tube simultaneously.

Still further in accordance with the first embodiment of the presentapplication, moving the catheter over the guide wire comprises movingthe catheter and the infusion tube simultaneously by the infusion tubesliding on the guide wire.

In accordance with a second embodiment of the present disclosure, thereis provided a catheter device for thrombus aspiration comprising: aninflatable member; a carrier catheter having a proximal end and a distalend adapted to be inserted percutaneously into an artery, the carriercatheter having a tubular body adjacent to a rear end of the inflatablemember; an inflating tube passing through the tubular body and having anopen front end in fluid communication with the inflatable member toinflate same; an infusion tube adapted to infuse pharmacologic agents,the infusion tube passing through the tubular body and having an openfront end extending beyond the inflatable member; and an aspiration tubeadapted to aspire the thrombus, the aspiration tube passing through thetubular body and having an open front end between the carrier catheterand the inflatable member.

Further in accordance with the second embodiment of the presentapplication, at least one radio-opaque marker is at a distal end of theinfusion tube.

Still further in accordance with the second embodiment of the presentapplication, at least one radio-opaque marker is on at least one of adistal end and a proximal end of the inflatable member.

Still further in accordance with the second embodiment of the presentapplication, said radio-opaque markers are at the distal end and theproximal end of the inflatable member.

Still further in accordance with the second embodiment of the presentapplication, a guide wire is received in the infusion tube.

Still further in accordance with the second embodiment of the presentapplication, a proximal end of the carrier catheter has a taperedprofile.

Still further in accordance with the second embodiment of the presentapplication, a proximal end of the aspiration tube is coterminous with aproximal end of the carrier catheter.

Still further in accordance with the second embodiment of the presentapplication, the proximal end of the carrier catheter has a taperedprofile.

Still further in accordance with the second embodiment of the presentapplication, the carrier catheter, the inflating tube, the infusion tubeand the aspiration tube are integrally connected to one another.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a catheter device for infusing apharmacologic agent and for thrombus aspiration in accordance with anembodiment of the present disclosure;

FIG. 2 is a schematic side view of the catheter device of FIG. 1;

FIG. 3 is a sectional view of a carrier catheter of the catheter deviceof FIG. 1;

FIG. 4 is a flowchart of a method for infusing a pharmacologic agent andperforming thrombus aspiration in accordance with another embodiment ofthe present disclosure

FIG. 5 is a flowchart of a method for infusing a pharmacologic agent andperforming thrombus aspiration in accordance with yet another embodimentof the present disclosure.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to the drawings and, more particularly, to FIG. 4, there isshown at 10 a method for performing thrombus aspiration in accordancewith an embodiment of the present disclosure. A catheter device that maybe used to infuse pharmacologic agents and perform thrombus aspirationaccording to the method is described hereinafter.

According to 12, with the thrombus (a.k.a., blood clot, plaque rupture,artery occlusion) being localized, a catheter device is inserted intothe coronary artery proximally of the artery occlusion, to be directeddistally in the artery toward the thrombus.

According to 14, an infusion tube of the catheter device is directedthrough the blood clot. One way to perform this step is to firstly passa guide wire through the blood clot. The infusion tube at the end of thecatheter device is subsequently guided along the guide wire in anover-the-wire fashion through the occlusion. Therefore, the tip of theinfusion tube of the catheter is distal of the blood clot afterinsertion.

The infusion tube may be localized by the presence of radio-opaquemarkers. Fluoroscopic imagery may be used to locate the infusion tuberelative to the thrombus in the treated artery.

According to 16, an inflatable member on the catheter device is inflatedproximally of the blood clot.

According to 18, a pharmacologic agent is infused into the infarctionzone distally of the occlusion. As the artery is blocked by theocclusion and the inflated member, the pharmacologic agent will diffuseand be absorbed locally, distal to the blood clot.

The infusion of the pharmacologic agent may also be performed prior tothe inflation of the inflatable member.

According to 20, the blood clot is vacuumed out of the artery so as toopen the artery. The aspiration tube of the catheter device isproximally positioned relative to the inflatable member. Hence, theinflatable member must be deflated prior to the aspiration, for theaspiration to be performed on the blood clot.

In one embodiment, the aspiration is initiated while the inflatablemember is inflated. This causes a relative negative pressure between thetip of the aspiration tube and the inflated member. When the inflatablemember is deflated, a sudden pressure drop will be created at thethrombus, ensuring that most of the blood clot is captured and aspiredout of the artery.

Subsequently, the various steps for terminating the intervention areperformed, including the removal of the various units of the catheterdevice. It is pointed out that the method 10 may be performed accordingto any suitable sequence.

Referring to FIGS. 1 to 3, a catheter device in accordance with thepresent disclosure is generally shown at 30. The catheter device 30 maybe used for the infusion of pharmacologic agents and for thrombusaspiration in accordance with the methodology described for method 10 ofFIG. 4, and method 50 of FIG. 5 as described hereinafter.

The catheter device 30 is introduced over a guide wire 31 (FIG. 2) thatis inserted into the coronary artery. The catheter device has ahydrophilic surface, so as to slide within the artery with reducedinvasiveness.

The catheter device 30 is then slid along the guide wire 31. A carriercatheter 34, also known as an outer jacket of the catheter device 30,has an hydrophilic surface. According to an embodiment, the carriercatheter 34 is made of polyether block amide (e.g., Pebax™ 5533). Asseen in FIG. 2, the front end of the aspiration tube of the carriercatheter 34 has a tapered profile to increase the aspiration area. Aninflatable member 36 may be positioned at the front end of the carriercatheter 34. The inflatable member 36 may be any suitable type ofinflatable material, such as a balloon. According to an embodiment, theinflatable member 36 is made of a substantially compliant membrane, soas to distribute inflating pressure uniformly on the inner surface ofthe artery.

Markers 38 of detectable material may be provided at one or bothextremities of the inflatable member 36 for localization thereof, and ata tip of an infusion tube 41 (FIG. 2). For instance, radio-opaquematerial may be used for fluoroscopic localization, such as platinumwith an iridium content (e.g., 10%). Alternatives are considered aswell. According to an embodiment, the markers 38 have an inner diameterof 0.023″, a wall of 0.001″ and an outside diameter of 0.025″.

Referring to FIG. 3, a section of the carrier catheter 34 is shown. Theinfusion tube 41 of the carrier catheter 34 has a passage 40 adapted toreceive the guide wire 31, and to infuse medication. The infusion tube41 itself is sized for the sliding displacement on the guide wire 31.The infusion tube 41 is subsequently used for infusion of pharmacologicagents, when the guide wire 31 is removed. The infusion tube 41 isopen-ended at the front end of the carrier catheter 34, and its tipprojects beyond the inflatable member 36. The infusion tube 41 mayconsist of any appropriate material. According to an embodiment, theinfusion tube 41 may be made from a single extruded material. However, acombination of layers may be considered as well, such as high-densitypolyethylene (e.g., HDPE LR734, 25%) and/or polyether block amide (e.g.,Pebax™ 7233, 75% of outer layer) and/or Plexar™ (e.g., middle layer ofPlexar™ 3080). As an example, the infusion tube 41 may have an innerdiameter of 0.018″, a wall thickness of 0.0020″ and an outer diameter of0.022″. Other dimensions are considered as well.

An inflating tube 43 is also part of the carrier catheter 34 and has alumen 42 opening into the inflatable member 36 at the front end of thecatheter device 30, for injection of a fluid into the inflatable member36 by the inflating tube 43 (although the inflatable member 36 could beinflated with any other of the tubes). According to an embodiment, theinflating tube 43 may be made from a single extruded material. However,a combination of layers may be considered as well, such as high-densitypolyethylene (e.g., HDPE LR734, 25%) and/or polyether block amide (e.g.,Pebax™ 7233, 75% of outer layer) and/or Plexar™ (e.g., middle layer ofPlexar™ 3080). As an example, the inflating tube 43 may have an innerdiameter of 0.018″, a wall thickness of 0.0020″ and an outer diameter of0.022″. Other dimensions are considered as well. Any appropriate type offluid may be used. For instance, a mixture of saline and iodine contrastis commonly used for inflating balloons in percutaneous coronaryintervention.

Still referring to FIG. 3, a passage 44 is also defined in the carriercatheter 34, and is part of an aspiration tube 45. The aspiration tube45 is open-ended at the front end of the carrier catheter 34, and may becoterminous therewith in the manner shown in FIG. 1. The open end of theaspiration tube 45 is offset relative to the open end of the infusiontube 41, and is hence proximally located in the artery relative to aposition of the inflatable member 36 and of the open end of the infusiontube 41. The aspiration tube 45 may be made from a combination oflayers, such as polytetrafluoroethylene, a stainless steel braid (e.g.,0.0005″ thickness for 0.005″ width of flat wire with 44 pics/in), and apolyether block amide lumen (e.g., Pebax™ 6333). As an example, theaspiration tube 45 may have an inner diameter of 0.040″, a wallthickness of 0.0025″ and an outer diameter of 0.045″. Other dimensionsare considered as well. According to an embodiment, apolytetrafluoroethylene (PTFE) tube is placed over a mandrel alsocovered with PTFE, and the stainless steel braid is then positioned onthe PTFE.

Markers may also be provided at the front end of the aspiration tube 45to localize the front end of the tube 45 relative to the blood clot,using any appropriate imaging technique.

The tubes 41, 43 and 45 emerge out of the proximal end of the carriercatheter 34, with their open external ends being outside of the body, soas to be connected to appropriate means. The tubes 41, 43 and/or 45 maybe equipped with suitable connectors (e.g., luers) for connection to thevarious devices (e.g., syringe). The infusion tube 41 is connected to asource of pharmacologic agents, such as a syringe, etc, for thecontrolled infusion of pharmacologic agents via the catheter device 30.As mentioned above, the inflating tube 43 is connected to a source offluid for pressurization of the inflatable member 36.

The aspiration tube 45 is connected to an aspiration mechanism, such asa vacuuming syringe or the like. Accordingly, an aspiration actionperformed at the external end of the aspiration tube 45 causes anaspiration at the open internal end of the aspiration tube 45. Asmentioned above, as the open internal end of the aspiration tube 45 ispositioned adjacent to the blood clot in the thrombus aspirationapplication, the blood clot is vacuumed away from the artery via theaspiration tube 45.

Any appropriate material may be used for the tubes. According to otherembodiments, the infusion tube 41 and the inflating tube 43 are, forinstance, made of polyimide of medical grade, or any other relativelycompliant material. One material that may be used for the aspirationtube 45 is braided reinforced polyimide, to ensure that the aspirationtube 45 maintains its structurally integrity despite the vacuumingpressure in the tube 45. During manufacturing, the outer jacket makingup the carrier catheter 34 may be slid over the tubes 41, 43 and 45.With the tubes 41, 43 and 45 fixed and aligned with the outer jacketthereon, they may be passed through a heated die, with the outer jacket34 fusing all together to give the shape of FIG. 3, or any otherappropriate shape. Hence, these components are integrally connected toone another.

Contemplated dimensions are set forth below, by way of example, and forillustrative purposes. It is understood that the dimensions may begreater or smaller than those set forth below. The dimensions are ininches.

The carrier catheter 34 has an oval section of 0.065×0.054. The innerand outer diameters of the infusion tube 41 are 0.018 and 0.022; theinner and outer diameters of the inflating tube 43 are 0.010 and 0.014;the inner and outer diameters of the aspiration tube 45 are 0.039 and0.043. The length of the inflatable member 36 is 0.200. All dimensionsare given as an example, and it is contemplated to provide theabove-referred components with a slight variation from these values.

Now that the catheter device 30 has been described, its use in athrombus aspiration application is described, according to the method 10of FIG. 4.

Referring concurrently to FIGS. 1 to 4, once the thrombus is localized,the guide wire is inserted into the coronary artery proximally of theartery occlusion, and is directed distally toward the thrombus, inaccordance with 12. The front end of the guide wire 31 passes throughthe thrombus.

According to 14, the catheter device 30, mounted onto the guide wire 31(with the guide wire being in the passage 40 of the infusion tube 41),is guided toward the blood clot by sliding engagement on the guide wire31. The tip of the infusion tube 41 of the catheter device 30 isdirected through the blood clot. Therefore, the open-ended tip of theinfusion tube 41 is distally located relative to the blood clot, whilethe inflatable member 36 is proximally located relative to the bloodclot. The guide wire 31 is then removed out of the artery.

The inflatable member 36 and/or the tip of the infusion tube 41 arelocalized in the artery, using the detectable markers 38. Fluoroscopicimagery or any other appropriate method may be used to locate themarkers 38 relative to the thrombus in the treated artery.

According to 16, the inflatable member 36 is inflated proximally to theblood clot. This is performed by injecting fluid into the open externalend of the inflating tube 43.

According to 18, the pharmacologic agent is infused in the infarctionzone distally of the occlusion, by the infusion tube 41 in the infusionpassage 40 now free of the guide wire (guide wire previously removed).As the artery is blocked by the occlusion, or the inflated balloon 36,the pharmacologic agent is absorbed locally.

The infusion of the pharmacologic agent may also be performed prior toinflating of the inflatable member 36.

According to 20, the blood clot is vacuumed out of the artery so as toopen the artery. The aspiration tube 45 is adjacent to the blood clot,but separated therefrom by the inflated member 36. The aspiration tube45 may be stiffened by a stylet for insertion of the carrier catheter 34into the artery. The stylet is thus removed prior to the aspiration. Anaspiration mechanism, such as a vacuuming syringe, is connected to theopen external end of the aspiration tube 45 to perform the thrombusaspiration, but with the deflating of the inflated member 36 performedright after aspiration is initiated, to create a sudden pressure drop atthe occlusion. Also, a back and forth motion of the catheter 30 willhelp to aspire the blood clot while the aspiration is performed.

The catheter device 30 may then be removed from the artery, and allnecessary steps are performed to complete the angioplasty.

Numerous pharmacologic agents may be used for the infusion, the doses ofwhich are selected on a case-by-case basis by appropriate personnel.Among the pharmacologic agents that can be used are: adenosine andadenosine receptor agonists, beta blockers, angiotensin-convertingenzyme inhibitor, angiotensin-receptor blockers, aldosterone, calciumchannel blockers (Verapamil, Diltiazem, Nifedipine), cyclosporin,calpain inhibitor, sodium-proton exchanger inhibitor, NO donor, cox-2inhibitor, statins, TNF-alpha, endothelin receptor antagonists,antiplatelet, antithrombotic, erythropoietin, anti-leukocyte complementinhibitors, opioid, anesthetic, K_(ATP) “openers”, insulin, thrombin andfragments, melatonin, H₂S, bradykinin, cellular therapy, gene therapy,with the proper catheter.

Referring to the drawings and, more particularly, to FIG. 5, there isshown at 50 yet another method for infusing a pharmacologic agent andfor performing thrombus aspiration in accordance with an embodiment ofthe present disclosure. The above-referred catheter device may be usedto perform the infusion of medication and thrombus aspiration accordingto the method 50 described hereinafter.

According to 52, with the thrombus (a.k.a., blood clot, plaque rupture,artery occlusion) being localized, a catheter device is inserted intothe coronary artery proximal to the artery occlusion, to be directeddistal to the artery toward the thrombus.

According to 54, an inflatable member of the catheter device, such as aballoon, is directed through the blood clot. One way to perform thisstep is to firstly pass a guide wire through the blood clot. Theinflatable member at the end of the catheter device is subsequentlyguided along the guide wire in an over-the-wire fashion through theplaque occlusion. Therefore, the inflatable member and a tip of thecatheter are distal to the blood clot.

There may be performed a step of localization of the inflatable member,for instance if detectable markers are provided in register with theinflatable member on the catheter device. Fluoroscopic imagery may beused to locate the inflatable member relative to the thrombus in thetreated artery.

According to 56, the inflatable member is inflated distal of the bloodclot. In doing so, microparticles of the thrombus are prevented frommoving distally by the presence of the inflatable member blocking theartery distal of the occlusion. Hence, the inflatable member providesdistal protection from embolization.

According to 58, a pharmacologic agent is infused into the infarctionzone beyond the occlusion and the inflated member, and thereforedownstream of the blood clot. As the artery is blocked by the inflatedmember, the pharmacologic agent is absorbed locally.

The infusion of the pharmacologic agent may be performed prior to theinflating of the inflatable member.

According to 60, the blood clot is vacuumed out of the artery so as toopen the artery. Any free microparticles are held in the artery upstreamof the inflated member, and thus vacuumed as well.

Subsequently, the various steps for terminating the intervention areperformed, including the removal of the catheter device. It is pointedout that the method 50 may be performed according to any suitablesequence.

The invention claimed is:
 1. A catheter device for thrombus aspirationcomprising: a carrier catheter having a proximal end and a distal endadapted to be inserted percutaneously into an artery, the carriercatheter forming an outer sheath of the catheter device and having atubular body; an inflatable member fixed to the carrier catheter; aninflating tube passing through the tubular body and having an open frontend in fluid communication with the inflatable member to inflate same;an infusion tube adapted to infuse pharmacologic agents, the infusiontube passing through the tubular body and having an open front endextending beyond the inflatable member; and an aspiration tube passingthrough the tubular body and having an open front end adapted to bepositioned proximally to the thrombus to aspire the thrombus, theinflating tube, the infusion tube and the aspiration tube being fixed tothe carrier catheter at the distal end of the carrier catheter.
 2. Thecatheter device of claim 1, further comprising at least one radio-opaquemarker at a distal end of the infusion tube.
 3. The catheter device ofclaim 1, further comprising at least one radio-opaque marker on at leastone of a distal end and a proximal end of the inflatable member.
 4. Thecatheter device of claim 3, comprising said radio-opaque markers at thedistal end and the proximal end of the inflatable member.
 5. Thecatheter device of claim 1, further comprising a guide wire, the guidewire being received in the infusion tube.
 6. The catheter device ofclaim 1, wherein a distal end of the carrier catheter has a taperedprofile.
 7. The catheter device of claim 1, wherein a distal end of theaspiration tube is coterminous with a distal end of the carriercatheter.
 8. The catheter device of claim 7, wherein the distal end ofthe carrier catheter has a tapered profile.
 9. The catheter device ofclaim 1, wherein the carrier catheter, the inflating tube, the infusiontube and the aspiration tube are integrally connected to one another.10. The catheter device of claim 1, wherein the aspiration tube has agreater diametrical dimension than the infusion tube and the inflatingtube.
 11. The catheter device of claim 10, wherein the aspiration tubehas an outer diameter of at most 0.043 in.
 12. The catheter device ofclaim 1, wherein the carrier catheter has an oval cross-sectional shape.13. The catheter device of claim 1, wherein the aspiration tube has anaxially-facing distal opening.
 14. The catheter device of claim 1,wherein the carrier catheter has three distinct passages in the tubularbody, whereby each of the inflating tube, the infusion tube and theaspiration tube is in a respective one of the passages.
 15. The catheterdevice of claim 1, wherein the inflating tube, the infusion tube and theaspiration tube are offset from a center of the carrier catheter.